RESUMO
BACKGROUND: 2,3-Dihydro-3,5-dihydroxy-6-methyl-4(H)-pyran-4-one (DDMP) and 5-hydroxymethylfurfural (HMF) are two main enolization products in the Maillard reaction and found in some foodstuffs. For many years, whether they are functional or noxious to human health has been a matter of debate. Thus, insight into their formation pathways is important to manage Maillard reaction products. In this study, DDMP and HMF were quantified and compared with regard to their formation and degradation in the d-glucose and l-proline Maillard reaction models using different moisture contents (0, 0.1, 0.5, 1.0, and 4.0 mL) at 150 °C for various heating times. RESULTS: DDMP was predominantly generated in dry or low water-content heating models along with n increased 1-deoxyglucosone (1-DG) generation via 2,3-enolization. However, increasing moisture content resulted in a decay of reaction intensity, 1-DG, and DDMP due to a change in the reaction mechanism from 2,3-enolization to 1,2-enolization, which facilitated 3-deoxyglucosone (3-DG) and HMF formation. CONCLUSION: Increased moisture content in glucose-proline models reduced reaction intensity and also inhibited DDMP and facilitated HMF formation by promoting the pathway change from 2,3-enolization to 1,2-enolization to generate more 3-DG. A water content of 1.0 mL was identified as a critical value, from which the 1,2-enolization became a primary pathway occurring in the Maillard reaction. © 2022 Society of Chemical Industry.
Assuntos
Glucose , Reação de Maillard , Humanos , Glucose/química , Prolina , Temperatura Alta , ÁguaRESUMO
BACKGROUND: Mesenchymal stem cells (MSCs) have been proved to drive castration resistant prostate cancer (CRPC). In this study, we aim to investigate the contribution of MSCs to the development of docetaxel resistance in CRPC cells and its potential mechanisms. METHODS: The effect of MSCs on CRPC cells resistance to docetaxel was determined using in vivo and in vitro approaches. CCK8 and PI/Annexin V-FITC assay were used to examined the cell viability and apoptosis. The concentration of transforming growth factor-ß1 was measured by enzyme-linked immunosorbent assay and small interfering RNA was used for functional analyses. RESULTS: MSCs significantly reduced the sensitivity of CRPC cells to docetaxel-induced proliferation inhibition and apoptosis promotion in vivo and in vitro. CRPC cells cocultured with MSCs under docetaxel administration have an increased autophagy activation, while autophagy inhibitor could effectively reversed MSCs-induced resistance to docetaxel. Additionally, MSCs-induced CRPC cell autophagy increase under docetaxel administration depends on MSCs secreting TGF-ß1 and inhibition of TGF-ß1 secretion in MSCs could consequently increase the sensitivity of CRPC cells to docetaxel. CONCLUSIONS: These results suggest that docetaxel administrated CRPC cells may elicit MSCs secreting TGF-ß1 increase, which desensitizes CRPC to docetaxel chemotherapy accelerating chemoresistance occurrence via inducing cell autophagy.
RESUMO
Stroke may cause severe death and disability but many clinical trials have failed in the past, partially because the lack of an effective method to regenerate new neurons after stroke. In this study, we report an in vivo neural regeneration approach through AAV NeuroD1-based gene therapy to repair damaged brains after ischemic stroke in adult non-human primates (NHPs). We demonstrate that ectopic expression of a neural transcription factor NeuroD1 in the reactive astrocytes after monkey cortical stroke can convert 90% of the infected astrocytes into neurons. Interestingly, astrocytes are not depleted in the NeuroD1-converted areas, consistent with the proliferative capability of astrocytes. Following ischemic stroke in monkey cortex, the NeuroD1-mediated astrocyte-to-neuron (AtN) conversion significantly increased local neuronal density, reduced microglia and macrophage, and surprisingly protected parvalbumin interneurons in the converted areas. Furthermore, the NeuroD1 gene therapy showed a broad time window in AtN conversion, from 10 to 30 days following ischemic stroke. The cortical astrocyte-converted neurons showed Tbr1+ cortical neuron identity, similar to our earlier findings in rodent animal models. Unexpectedly, NeuroD1 expression in converted neurons showed a significant decrease after 6 months of viral infection, indicating a downregulation of NeuroD1 after neuronal maturation in adult NHPs. These results suggest that in vivo cell conversion through NeuroD1-based gene therapy may be an effective approach to regenerate new neurons for tissue repair in adult primate brains.
